Cardiac surgical procedures for treatment of refractory ventricular arrhythmias are most successful when identifiable regional ventricular dyskinesia is present. The purpose of this research project is to assess the basis for this observation by evaluating the contribution of abnormal regional ventricular wall motion to alterations of electrophysiological properties in normal and ischemic canine myocardium. Using signals from paired ultrasonic dimension transducers within the left ventricular wall and electrograms from epicardial and transmural electrodes, regional myocardial systolic function and electrophysilogical properties will be assessed simultaneously in instrumented awake dogs. Four series of experiments are planned. First, graded coronary artery occlusion will be used to induce wall motion abnornalities; and regional systolic function, electrophysiological parameters, and blood flow (microsphere technique) will be measured in ischemic and normal zones. Varied degrees of aortic constriction will be used to potentiate wall motion disturbances, and measurements will be repeated. A second series of dogs will be studied 2-3 weeks following myocardial infarction induced by total coronary artery occlusion while a thrid series of dogs will be studied following development of ventricular aneurysm by combined myocardial ischemia and low-protein diet. Finally, since calcium influx may be responsible for mechanically-induced electrophysiological changes, a fourther series of dogs will be studied in which graded regional wall motion abnormalities will be induced by papillary muscle traction in the presence and absence of verapamil (75 and 150 g/kg, IV). In all studies, the relation between levels of diminished altered myocardial mechanical dysfunction and electrophysiological changes at known levels of diminished regional blood flow will be correlated by computer-based multivariate analysis. Thus, electrophysiological changes induced by wall motion abnormalities alone will be defined. In summary, this project will evaluate the clinically important relationship between regional abnormalities in ventricular wall motion and ddevelopment of potentially arrhythmogenic alterations in myocardial tissue. The results may be directly applicable to both medical and surgical treatment of patients in whom localized ventricular wall motion disturbances are associated with life-threatening ventricular arrhythmias.